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Limitations:Patients were referred from primary care to a single-center rhinology clinic, which limits the generalizability of results. Serial measurements of surrogates of nasal inflammation (such as nitric oxide or cytokine levels) were not performed.

Conclusion:Initial oral steroid therapy followed by topical steroid therapy seems to be more effective over 6 months than topical steroid therapy alone in decreasing polyp size and improving olfaction in patients referred for specialty care of CRS with at least moderate nasal polyposis.

Primary Funding Source:Chief Scientist Office, Scotland; National Health Service Tayside Small Grants Scheme; and an Anonymous Trust grant from University of Dundee.

Editors' Notes

Context

Chronic rhinosinusitis with nasal polyposis is a common problem resulting in nasal blockage, facial pain, and hyposmia. Responses to therapy are frequently incomplete, and relapses are common. Although oral steroids are recommended only when specialty care is required, little is known about their efficacy.

Contribution

Patients with at least moderate-sized nasal polyps and chronic rhinosinusitis were randomly assigned to receive 2 weeks of therapy with oral steroids or placebo, followed in both groups by sequential steroid nasal drops and spray. Over 28 weeks of therapy, a greater reduction in the size of polyps and greater improvement in olfaction were observed after induction therapy with oral steroids.

Caution

The diagnosis of chronic rhinosinusitis with nasal polyposis was made by otorhinolaryngologists at a specialty clinic, and the applicability of these findings to patients seen only in primary care is unclear.

Implication

An initial course of oral steroids seems to be effective in reducing polyp size and improving olfaction in some patients with chronic rhinosinusitis and nasal polyps.

—The Editors

Chronic rhinosinusitis (CRS) is one of the most common chronic disorders in the developed world, affecting 32 million persons (16.3% of the population) in the United States alone (1). Annual health care costs for CRS are estimated at $6 billion, which is probably an underestimate because of the indirect costs from lost productivity and the effect on general and lower airway health outcomes (1–3). Chronic rhinosinusitis with nasal polyposis, a distinct pathologic subtype of CRS with an estimated prevalence of 3% to 5%, has a greater burden of symptoms and a higher relapse rate after treatment (4–5). This condition is managed by various practitioners, including primary care physicians, otolaryngologists, respiratory physicians, and allergologists.

Despite the high prevalence and significant morbidity associated with CRS with nasal polyposis, evidence to guide practitioners on initiation and maintenance of therapy is limited. Current international guidelines (5) recommend that primary care physicians diagnose CRS with nasal polyposis on the basis of such symptoms as nasal blockage, discharge, facial pain or pressure, and reduction in the sense of smell for more than 12 weeks. Topical steroids are recommended for CRS, with or without nasal polyposis, along with nasal saline douching and antiallergy medications as needed (5). Referral to an otolaryngologist is recommended if no response is observed after 3 months of these treatments. Under these guidelines, oral steroids are reserved for use by otolaryngologists, and only for severe CRS with nasal polyposis or for refractory cases (2, 5).

Monotherapy with intranasal corticosteroids can lead to a steady loss of symptom control in the long term (6–8). Chronic rhinosinusitis with nasal polyposis is characterized by frequent relapses, which prompt repeated referrals to secondary care for rescue therapy (5). We hypothesize that this is partly attributable to the inability of topical therapies to effectively penetrate the ostiomeatal complex (the outflow tract of the paranasal sinuses) and reestablish physiologic sinus drainage. Surgical treatment temporarily relieves ostiomeatal complex blockage, but it is not curative and serves primarily to facilitate the penetration of topical steroid therapy. In addition, surgery should be reserved for cases that are refractory to maximum medical therapy because of the potential for orbital and intracranial complications (5). A short course of oral steroids, known as medical polypectomy, might improve the long-term efficacy of topical therapy; however, data to support this practice are lacking. Furthermore, despite the high prevalence of concomitant asthma and use of inhaled corticosteroids, no data on long-term systemic steroid burden in these patients are available.

We hypothesized that initial therapy with oral steroids would lead to a greater and sustained reduction in polyp size and an improvement in olfaction, nasal airflow, and quality-of-life variables. On this basis, we conducted the first randomized clinical trial to evaluate the efficacy and safety of a treatment regimen that comprised a 2-week course of oral steroids followed by a 26-week course of intranasal steroids.

Methods

We conducted a parallel, randomized, controlled trial in which patients who had CRS with nasal polyposis received either oral prednisolone or placebo for the first 2 weeks, followed in both groups by fluticasone nasal drops for 8 weeks and then fluticasone nasal spray for 18 weeks.

Setting and Participants

We recruited nonsmoking adults who had CRS with nasal polyposis, with or without asthma, from a single-center specialty clinic in Tayside, Scotland, to which patients were referred for assessment by their primary care physicians. Ear, nose, and throat specialists diagnosed CRS with nasal polyposis on the basis of the European Position Paper on Rhinosinusitis and Nasal Polyps 2007 criteria (5). Inclusion criteria were the presence on nasoendoscopy of bilateral moderate-sized to large nasal polyps (grade >1) according to the Lildholdt scale (0, no nasal polyps; 1, small polyps confined to the middle meatus; 2, moderate-sized polyps not crossing the lower edge of the inferior turbinate; 3, large polyps crossing the lower edge of the inferior turbinate) (9) and at least 2 of anterior or posterior nasal discharge, nasal obstruction, or decreased sense of smell for more than 12 weeks. Exclusion criteria included treatment with an oral corticosteroid in the past 3 months, sinus surgery in the past year, recent upper respiratory tract infection, mechanical nasal airway obstruction of more than 50% due to septal deviation, or pregnancy or lactation. The institutional review board of the Tayside Committee on Medical Research Ethics approved our study, and all participants gave written informed consent.

Our study was conducted in accordance with the current revision of the 1964 Declaration of Helsinki and guidelines laid down by the International Conference on Harmonization for good clinical practice in clinical trials. Serious adverse events were defined as noted in Appendix Table 1.

Random Assignment and Interventions

An independent, off-site clinical trials pharmacist (Pharmacy Production Unit, Western Infirmary, Glasgow, United Kingdom) used a computer-generated random allocation sequence to randomize the trial, using block randomization with a block size of 4. The same pharmacist masked and blinded the 25-mg prednisolone tablet and an identical placebo tablet to double-blind the study from the investigator and participants. Tablets were distributed in sealed opaque envelopes at the research unit, in sequential order, by a laboratory technician who was not directly involved with the study.

After a screening visit, eligible patients entered a 2-week period during which therapy for CRS with nasal polyposis was stopped. Patients were randomly allocated in a 1:1 ratio to receive either prednisolone, 25 mg/d, or an identical placebo for 2 weeks, followed in both groups by fluticasone propionate nasal drops (Flixonase nasule, Allen & Hanburys, Uxbridge, United Kingdom), 400 µg twice daily, for 8 weeks and then fluticasone propionate nasal spray (Flixonase nasal spray, Allen & Hanburys), 200 µg twice daily, for a further 18 weeks. From screening until the end of the study, no other rhinitis medications were permitted, including antihistamines, leukotriene receptor antagonists, intranasal corticosteroids, or nasal decongestants. No antibiotics were permitted during the study.

Outcomes and Measurements

Baseline Measurements

To characterize upper and lower airway disease and identify potential predictive factors that could influence therapeutic effectiveness, we established the presence and severity of asthma by history, spirometry (SuperSpiro, Micro Medical, Chatham Maritime, United Kingdom) (10), body plethysmography (Jaeger MasterScreen, CareFusion, Basingstoke, United Kingdom) (11), tidal and nasal nitric oxide levels (Niox, Aerocrine, Solna, Sweden) (12), and bronchial methacholine challenge (13). Aspirin sensitivity was diagnosed by history and nasal lysine–aspirin challenge (14). The extent of rhinosinusitis was staged by using the modified Lund–Mackay system to score computed tomography scans of the paranasal sinuses on the basis of reconstructed axial and coronal sections (15); percentage of opacification was scored for each of the maxillary, frontal, anterior ethmoid, posterior ethmoid, and sphenoid sinuses as 0%, 1 (1% to 25%), 2 (26% to 50%), 3 (51% to 75%), 4 (76% to 99%), or 5 (100%), and the scores were summed for each patient. Atopy was evaluated by total serum IgE levels and by radioallergosorbent testing for specific IgE to grass pollen, house dust mites, cats, dogs, or Aspergillus and IgG to Aspergillus. Polyp biopsies were performed to determine tissue eosinophil count. Specific levels of IgE to serum Staphylococcus aureus enterotoxins A and B and toxic shock syndrome toxin 1 were also measured with the UniCAP assay (Phadia, Uppsala, Sweden); the interassay coefficient of variation was 4.3%.

Longitudinal Measurements

Primary and secondary efficacy and safety outcomes were measured at random assignment (baseline) and after each treatment period (2, 10, and 28 weeks from baseline).

Sample Size

We estimated that with a parallel design and a sample size of 30 participants in each group, our study would be powered at greater than 90%, with a 2-tailed α value of 0.05, to detect a 0.5-unit difference in polyp grading between randomized treatments at 2 weeks (assumed SD, 0.4) (19). This would also provide greater than 90% power to detect a 6-mm improvement (minimal important difference) in the hyposmia visual analogue scale score. Minimal important differences were estimated to be 1 unit for polyp grading and 6 mm on the hyposmia visual analogue scale, on the basis of consensus and the Cohen small effect size, respectively (20).

Statistical Analysis

We included all patients who received the allocated intervention in the analysis. To estimate overall treatment effects between groups, repeated-measures outcomes were analyzed by using random-effects models. These allow for the correlation of measurements over time and allow some measurements to be missing, assuming they are missing at random. The effect of time was modeled with polynomials, and the best fit was obtained by using the Akaike Information Criterion. This criterion was also used to assess random intercepts and random slopes in all models. All models were adjusted for age and sex. Safety outcomes were also adjusted for baseline. The outcomes were assessed for deviations from normal distributions, and suitable transformations were applied. Model-based predicted means were calculated by fitting treatment-by-time interactions, and all random-effects models were implemented by using the PROC MIXED command in SAS, version 9.1 (SAS Institute, Cary, North Carolina). In the random-effects models, time (in weeks) was found to fit a cubic best (smallest Akaike Information Criterion), along with random intercepts and random coefficients. Most outcomes, including the primary outcome of polyp grading, had a reasonably normal distribution. Natural log transformations were applied to the results of overnight urinary cortisol corrected for creatinine, total nasal symptom score, and assays for serum high-sensitivity C-reactive protein and serum procollagen-1 N-terminal peptide. The square-root transformation worked best for the mini-RQLQ, and the reciprocal worked best for serum procollagen-3 N-terminal peptide assay results. The number of missing measurements varied by outcome, with 7% missing for the main outcome; this is small and unlikely to introduce major biases.

Participants in either treatment group who had an improvement of more than 1 minimal important difference in either polyp grading or hyposmia visual analogue scale at the end of 6 months were classified as responders. Minimal important differences are described elsewhere (17–18) for the mini-RQLQ (0.7 unit), peak nasal inspiratory flow (6 L/min), and total nasal symptom score (0.55 units) but were not used to estimate response. Responders and nonresponders were compared by using unpaired t tests for all interval variables and Pearson chi-square tests for categorical data for oral steroid induction, age, duration of rhinitis, previous sinus surgery, historical and challenge-based aspirin intolerance, serum IgE level, systemic and tissue eosinophilia, presence of asthma, spirometry, body plethysmography, bronchial methacholine challenge, nasal and tidal nitric oxide level, and paranasal sinus computed tomography scan scores.

Role of the Funding Source

This study was funded by the Chief Scientist Office, Scotland; National Health Service Tayside Small Grants Scheme; and an Anonymous Trust grant from the University of Dundee. The funding sources were not involved in the study design, data collection, interpretation, or writing of the report.

Results

We conducted our study from January 2005 to February 2008. Of the 118 patients screened, 60 were randomly assigned and 51 completed the study (Figure 1). Three patients in the prednisolone group and 4 in the placebo group had previously received oral steroids; in these patients, steroid therapy was last given a mean of 14 months (range, 6 to 24 months) and 12 months (range, 8 to 18 months), respectively, before recruitment. Similarly, 9 patients in the prednisolone group and 10 in the placebo group had previously received oral antibiotics; this therapy was last given 17 months (range, 2 to 30 months) and 14 months (range, 3 to 25 months), respectively, before recruitment. Baseline characteristics, including demographic characteristics; disease duration; upper and lower airway inflammation; airway caliber; and indexes of severity, such as aspirin sensitivity, atopy, and asthma, were similar in both treatment groups (Table 1).

Efficacy Outcomes

Table 2 and Figure 2 present values at each time point, and changes in primary and secondary efficacy outcomes. In the prednisolone group, 3% of the data for polyp grading were missing at 2 weeks, 7% at 10 weeks, and 4% at 28 weeks, whereas in the placebo group, 7% of the data were missing at 2 weeks, 7% at 10 weeks, and 4% at 28 weeks. The mean decrease in polyp grade from baseline to 2 weeks was 2.1 units (SD, 1.1) for the prednisolone group and 0.1 unit (SD, 1.0) for the placebo group (mean difference between groups, −1.8 units [95% CI, −2.4 to −1.2 units]; P < 0.001). The difference between groups was −1.08 units (CI, −1.74 to −0.42 unit; P = 0.001) at 10 weeks and −0.8 unit (CI, −1.8 to 0.2 unit; P = 0.11) at 28 weeks. The mean decrease in hyposmia score from baseline to 2 weeks was 31.12 mm (SD, 30.1) in the prednisolone group and 1.41 mm (SD, 30.6) in the placebo group (mean difference between groups, −28.33 mm [CI, −42.71 to −13.96 mm]; P = 0.002). The difference between groups was −16.06 mm (CI, −30.99 to −1.13 mm; P = 0.03) at 10 weeks and −12.13 mm (CI, −30.55 to 6.29 mm; P = 0.19) at 28 weeks.

Table Jump PlaceholderTable 2.
Overall Treatment Effect From Mixed Models and Comparisons at Each Time Point for Efficacy Outcomes

Baseline characteristics did not differ between responders and nonresponders (Appendix Table 3). Twenty-five participants (83%) in the prednisolone group improved by more than the minimal important difference in either polyp grade or hyposmia visual analogue scale at the end of 28 weeks compared with 17 participants (57%) in the placebo group. Oral prednisolone therapy did not change levels of S. aureus enterotoxin–specific IgE (P > 0.05).

Safety Outcomes

After random assignment, 1 participant withdrew because of nausea and 1 had an asthma exacerbation (listed as “other medical reasons” in Figure 1). Thirty-seven participants (19 in the prednisolone group and 18 in the placebo group) reported an adverse event. Adverse events did not differ between groups (Appendix Table 1). No adverse events defined as serious by our protocol were reported. Basal and dynamic adrenal function were suppressed by oral prednisolone but recovered after the switch to nasal drops (Table 3 and Figure 2). Overnight urinary cortisol corrected for creatinine was suppressed to 50% and adrenocorticotropic hormone–stimulated serum cortisol to 86% of baseline values after 2 weeks of oral prednisolone therapy. At 10 and 28 weeks, however, no significant residual adrenal suppression (compared with baseline) was observed. Markers of osteoblast activity showed a similar transient decrement during oral steroid therapy, with a return to baseline with subsequent topical treatment (Table 3).

Table Jump PlaceholderTable 3.
Overall Treatment Effect From Mixed Models and Comparisons at Each Time Point for Safety Outcomes

Discussion

Our single-center study shows that in patients with CRS with nasal polyposis (polyp grade >1), an initial 2 weeks of oral prednisolone therapy significantly improves polyp size and hyposmia score compared with placebo. Benefits remained evident at 28 weeks without an increase in adverse steroid effects. Clinical markers of severity, such as aspirin intolerance, atopy, duration of illness, and concomitant asthma, did not differ between responders and nonresponders.

To our knowledge, no previous randomized, controlled trial has evaluated the long-term effects of oral steroid therapy for CRS with nasal polyposis. Previous studies have either lacked placebo control or were short-term only. In a trial by Benítez and colleagues (21), 63 participants who received oral prednisolone therapy for 2 weeks, tapered from an initial dose of 30 mg/d, followed by intranasal budesonide, 400 µg, for 12 weeks showed overall symptom improvement, whereas the 21 participants in the control group received no treatment over a 2-week period and were not followed afterwards. In a 2-week randomized, controlled trial, Hissaria and colleagues (22) evaluated the efficacy of oral prednisolone, 50 mg, versus placebo for CRS with nasal polyposis. Neither trial specifically examined the role of oral steroid therapy in improving the efficacy of subsequent long-term topical steroids or comprehensively evaluated efficacy or safety.

We chose an oral prednisolone dosage of 25 mg/d because it provides a good systemic anti-inflammatory effect and is available as a single, once-daily tablet. This regimen is frequently used in our clinical practice to aid adherence and reduce the potential side effects of higher doses, such as sleep disturbance. Of note, no adverse events attributable to oral steroids were reported in our study. We hypothesized that improvement in outcomes of CRS with nasal polyposis disease would require adequate clearance of the ostiomeatal complex, and therefore the initial steroid therapy was followed by 8 weeks of intranasal drop therapy. Nasal drops provide better deposition to the ostiomeatal complex and have lower systemic bioavailability than nasal sprays (23–24); however, they are relatively expensive and not universally available. For this reason, patients were maintained on therapy with intranasal spray for the remainder of the study.

Our study demonstrates a parallel and sustained improvement in both polyp size and the hyposmia visual analogue scale score, as seen in the short-term study by Hissaria and colleagues (22). Improved olfaction was also supported by the results of the Pocket Smell Test in the prednisolone group, although this did not reach statistical significance between groups. Nasal obstruction and hyposmia are the 2 primary symptoms of CRS with nasal polyposis, and they substantially affect quality of life (5, 25). Chronic rhinosinusitis with nasal polyposis causes olfactory impairment from mechanical obstruction and sensorineural defects secondary to mucosal inflammation (26). Although evidence indicates that oral steroids have a direct stimulatory effect on olfactory neurons, the sustained improvement in olfaction that we observed suggests that a reduction in local mucosal inflammation and edema is a more likely mechanism. We also found reductions in systemic markers of eosinophil activation (eosinophil-derived neurotoxin) and inflammation (high-sensitivity C-reactive protein) with systemic but not topical corticosteroid therapy, which further supports our hypothesis that the reduction in polyp size and improved sense of smell was due to local anti-inflammatory effects rather than systemic steroid spillover.

Although we demonstrated additional long-term efficacy with initial oral steroid therapy, this must be weighed against potential adverse steroid effects. In keeping with other series, more than 50% of our cohort had concomitant asthma treated with inhaled corticosteroids (5). To our knowledge, no long-term studies have evaluated the hypothalamic–pituitary–adrenal axis or bone turnover in patients who have CRS with nasal polyposis. However, it is reassuring that we found no residual adrenal suppression or reduction in osteoblast activity with our treatment regimen at 10 or 28 weeks.

Our study has limitations. We did not perform serial measurements of nasal inflammation by using surrogates, such as nitric oxide, eosinophils in repeated biopsy specimens, or cytokines obtained from nasal lavage. Although many studies describe these measures, their clinical relevance remains unclear (5, 27–28). Instead, a clinically meaningful set of subjective, objective, and quality-of-life efficacy outcomes were used. Ostiomeatal complex assessment with serial computed tomography would have been desirable. However, this does not reflect routine clinical practice in the United Kingdom; most patients who have CRS with nasal polyposis are treated in primary care, where such investigations are not readily accessible. Serial scanning would also expose patients to excessive radiation doses and provide little more clinical information than polyp grading. The Juniper mini-RQLQ was used as a quality-of-life assessment tool, in conjunction with a hyposmia visual analogue scale. The mini-RQLQ is a validated, reliable instrument that is shorter and easier to administer than more extensive, disease-specific measures, such as the 31-item Rhinosinusitis Outcome Measure (22). The mini-RQLQ was also considered to be a comprehensive means of evaluating quality of life, because 50% of our patients were atopic. Although our study size was sufficient to demonstrate many benefits of steroid therapy in the setting of a single referral center, larger, multicenter trials with longer follow-up are warranted.

Future studies should consider whether an induction and maintenance approach should be considered at the point of first diagnosis of CRS with nasal polyposis (for example, in primary care) and whether it is beneficial in milder disease, in which ostiomeatal complex obstruction is less severe. Short-term nasal decongestants may further improve access of intranasal corticosteroids and could be assessed alone or in conjunction with prednisolone induction. Finally, larger long-term studies are required to assess whether steroid induction can delay or reduce the need for surgical intervention and influence postsurgical recurrence rates.

In conclusion, we found that an initial 2-week course of oral steroid therapy followed by topical steroids seems more effective over 28 weeks than topical therapy alone in decreasing polyp size and improving olfaction for the treatment of CRS with nasal polyposis above grade 1, without sustained adverse effects. Although further research is required to assess the efficacy and safety of this approach in other settings, we believe these results are an important step in developing robust treatment approaches for this common but relatively understudied condition.

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Asthma and Allergy Research Group, Division of Cardiovascular and Lung Biology, University of Dundee

Conflict of Interest:
None Declared

We thank Mullol and colleague for bringing to prominence a much ignored but debilitating illness. We would like to take the opportunity to discuss several points raised by the editorial.

First, the editorial proposes that differences between groups in the co-primary outcomes of polyp size and olfaction do not endure at 28 weeks. Our interpretation of the data is that there are significant overall differences over the 28 week period of -1.1 units (-1.5, -0.6; <0.001) for polyp score and 15.40mm (-25.85, -4.95; 0.004) for hyposmia score (Table 2). These differences were calculated post hoc as requested by the journal using a longitudinal mixed model analysis (see methods). Moreover, this interpretation was supported using the a priori analysis of an ANCOVA: the differences between groups at 28 weeks were -0.9 units (-1.7 - - -0.1; 0.04) and P < 0.02 for hyposmia score (95%CI not calculable as a square-root transform was applied). We feel it is imperative not to ignore the significant overall trend between groups over the entire treatment period due to a P value falling on the 'wrong' side of an arbitrary numeral. Of course further research is needed before generalizability of this study can be fully understood. But the data show a significant difference over the entire study period.

Second, our study did not evaluate combined oral and topical steroids but sequential therapy. While combined therapy in patients with nasal polyposis may cause significant side-effects due to additive overall steroid burden, we have demonstrated there is no lasting effect on HPA axis or osteoblastic activity in patients treated sequentially. Indeed, almost 50% of our subjects had asthma and were on inhaled corticosteroids. With this in mind, it is unclear why the editorial recommends a 3 month trial of intranasal corticosteroids in patients with moderate to large sized nasal polyps. This approach was not supported by our data and we believe patients with this severity of disease will inevitable have some degree of ostiomeatal complex obstruction, which is the principal cause for disease perpetuation. Nasal steroid sprays do not relieve this obstruction and we routinely and safely treat patients with grade 2 and 3 polyps with an initial oral steroid burst followed by sequential topical therapy in the form of nasal drops and then spray. Using a tapered oral dosing regimen may not provide any benefit as there is a long experience in the UK of treating patients with asthma and COPD with a single daily dose of 25-50 mg without tapering. If anything, a tapering approach could lead to prolonged steroid exposure with increased risk of long term harm. Of course, no trial result will or should replace judicious clinical assessment of each individual patient by their physician. We also acknowledge that our patients were a selected cohort from a specialty clinic and that approach may not be applicable to patients with milder disease.

Third, we agree that there may be a loss of efficacy when switching from drops to nasal spray. While availability of nasal drops is not universal and they are more expensive; in our clinical practice in patients with severe disease we routinely step down therapy from fluticasone nasal drops 400 mcg bid to 200 mcg bid rather than switching to sprays. Nasal drops have been shown in cadaveric studies to access the middle meatus rather than nasal spray which mainly deposits on the inferior turbinates. Nasal drops also have lower systemic bioavailability in head to head comparison with nasal sprays.

Conflict of Interest:

Authors of the above article.

Suggestion for More Rigorous Allergy Testing and More Information Concerning Aspirin-Allergic Patients

Posted on
March 10, 2011

Adrian G. Letz

Mike O'Callaghan Federal Hospital

Conflict of Interest:
None Declared

TO THE EDITOR: Vaidyanathan and colleagues have provided useful information showing the efficacy of providing a burst of systemic corticosteroids for chronic rhinosinusitis (CRS) with nasal polyps along with continuing intranasal corticosteroids.

As a specialist who sees many CRS patients who have already had > 12 weeks of symptoms by the time they see me, providing a burst of oral corticosteroids, in addition to intranasal corticosteroids, has been my practice. It is reassuring to see that this approach is safe and efficacious in a double-blinded, randomized trial.

The authors completed a thorough investigation of baseline characteristics, but I would suggest that more rigorous allergy testing would have provided even more useful information. The presence of atopy was assessed by total serum IgE level along with radioallergosorbent testing for specific IgE to grass pollen, house dust mite, cat, and dog. True allergic rhinitis requires both the presence of symptoms elicited by a specific substance (for example, rhinitis during grass pollen season or perennial symptoms if allergic to house dust mite) along with specific IgE demonstrated to that substance. Individual patient histories with attention to seasonality of symptoms along with allergen skin prick testing would have better delineated any allergic component of these patients' CRS (1).

The presence of aspirin allergy was studied, and I am curious how history of aspirin intolerance was assessed. Approximately 50% in each study group had a positive nasal lysine-aspirin challenge, but only 23% in the prednisolone group and 20% in the placebo group had a "history of aspirin intolerance." Aspirin-exacerbated respiratory disease (or Samter's triad) is important to address in CRS patients, because formal aspirin challenge and desensitization with continuation of aspirin therapy can afford long-term symptom relief and reduction of courses of oral corticosteroids (2). Cystic fibrosis is another important condition to rule-out in patients with CRS with nasal polyps.

In conclusion, despite the European guidelines cited by the authors, it is entirely reasonable for a primary care physician to provide a course of oral corticosteroids for CRS patients while they are waiting to see a specialist.

Conflict of Interest:

Re:Suggestion for More Rigorous Allergy Testing and More Information Concerning Aspirin-Allergic Patients

Posted on
March 11, 2011

Sriram Vaidyanathan

Asthma and Allergy Research Group, University of Dundee

Conflict of Interest:
None Declared

To The Editor

We would like to thank Dr Letz for his comment and agree completely that it is not only safe but also important to commence a short burst of oral steroids in patients with nasal polyposis at the outset to improve the efficacy of subsequent topical therapy.

All our patients underwent a comprehensive assessment including a full history, medical examination, total nasal symptoms score, Juniper mini-RQLQ, RAST for the four common aeroallergens, Aspergillus IgG, total serum IgE, Staphylococcus aureus enterotoxin levels. (Methods) While skin prick testing is more sensitive than serum specific IgE, it is less specific[1]. Thus in nasal polyposis, where traditionally the role of allergy has been questioned, skin prick testing on its own adds nothing to RAST testing[2]. Moreover, the role of allergen immunotherapy and anti- histamines in the treatment of polyps is not established.

Our patients were classed as having a positive history only in the presence of clear symptoms suggestive of aspirin intolerance or medical records to prove the same. The role of routine aspirin sensitivity testing in the absence of clear symptoms of intolerance is unclear i.e. it is unlikely that an asymptomatic patient with a positive aspirin challenge would be treated with desensitization.

In a study (unpublished) we conducted in 75 patients with known aspirin intolerance and a positive aspirin challenge test, we found no increase in disease severity in those with a positive test but absent symptoms. We also found that in symptomatic patients with a history of aspirin intolerance, a longer duration of rhinitis and low FEF25-75 were more likely to have a positive challenge test.

Lastly, our patients were too old to have cystic fibrosis, although we didn't test for CF genes per se.

Conflict of Interest:

Summary for Patients

The full report is titled “Treatment of Chronic Rhinosinusitis With Nasal Polyposis With Oral Steroids Followed by Topical Steroids. A Randomized Trial.” It is in the 1 March 2011 issue of Annals of Internal Medicine (volume 154, pages 293-302). The authors are S. Vaidyanathan, M. Barnes, P. Williamson, P. Hopkinson, P.T. Donnan, and B. Lipworth.

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